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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus affects the mental health of many. Isolation, fear of infection, and social distancing may affect psychological functioning. Research continues to evolve and reveal the psychological symptoms reported by coronavirus disease 2019 (COVID-19) patients. Depression, anxiety, posttraumatic stress disorder (PTSD), and psychosis have been reported in the literature for COVID-19 patients. Potential preliminary treatment recommendations include various forms of psychotherapy, such as dialectical behavioral therapy, mindfulness-based cognitive therapy, and cognitive behavioral therapy. More research should be done regarding other additional treatment recommendations that may facilitate psychological healing in COVID-19 patients.

The assessment of visual impairment using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Fifth Edition, requires a thoughtful ophthalmologic evaluation and careful application of the functional vision tests and arithmetic criteria provided in Chapter 12, The Visual System, and other chapters, as applicable. The interpolation of the multiple dimensions of the visual system into the enumeration of a single impairment percentage may involve complex mathematical manipulations. Properly enumerated, the value can be utilized rigorously in impairment evaluations, functional evaluations, and even for academic research.

It is critical for brain death diagnosis to be accurate. Although standardized guidelines and institutional protocols for brain death determination exist, for many physicians, lack of understanding about brain death leads to confusion and muddles interactions with patients' loved ones at the end of life. Using a case-based approach, this article demonstrates what tends to go wrong in erroneous brain death diagnoses and clarifies what physicians and educators should do to help avoid these errors.

We present a case involving a catastrophic injury that resulted from a completely obstructed airway when an examinee choked on food. She had cardiopulmonary arrest and developed a hypoxic-ischemic encephalopathy associated with profound neurological losses. The evaluation of the consequences of severe central nervous system injury necessitates evaluation and rating of all the sequelae of that injury. The first step is clinical assessment, followed by thoughtful application of these data to the processes and criteria provided in the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides). The approaches discussed in the fifth and sixth editions of the AMA Guides are similar.

If both art and laughter are good for your health, why aren't we encouraging more humor in museums and hospitals? We are taught to approach art with awe and respect-and to treat medicine as deadly serious business. It follows, then, that overt displays of humor, such as laughing or joking in a museum, doctor's office, or hospital, are probably in bad taste. But if viewing and making art can lower rates of anxiety and depression and help soothe chronic pain-and if laughter helps blood vessels function better and improves the flow of oxygen to the heart and brain-then perhaps we unwittingly deprive our patrons and patients of an important tool in the health and wellness toolbox.

In the case scenario, RJ is a resettled refugee teenager who presents to his physician with vitamin B12 deficiency, anemia, and symptoms of mental illness. This commentary considers social determinants of refugee health and the moral importance of freedom to achieve well-being. The capabilities framework is used to analyze this case because it offers an ethical framework for understanding and evaluating social determinants of refugee health that either promote or diminish freedom to achieve well-being. By using this framework to consider social isolation as a negative social determinant of refugee health, clinicians and institutions can be caregivers as well as advocates for social justice, fulfilling 2 core ethical obligations to refugee communities.

Physicians often must evaluate patients who present with symptoms in a median nerve distribution and typically diagnose carpal tunnel syndrome (CTS), but an accurate diagnosis is critical to determine causation and to define possible impairment. CTS is a constellation of symptoms and signs that result from mononeuropathy of the median nerve in the carpal tunnel; symptoms typically include tingling and/or numbness, dysesthesias, and/or pain in the radial palm and palmar aspect of the thumb, index, middle, and perhaps ring fingers. The American Academy of Orthopaedic Surgeons suggests use of the CTS-6 scoring aid (shown in a table) as a clinical aid for diagnosing CTS. Electrodiagnostic testing, nerve conduction studies in particular, are considered the gold standard for diagnosis of CTS, but research suggests that the definitions of relevant sensory and assignment of CTS are sensitive to threshold changes from a latency of, eg, >4.4 msec vs >4.5 msec. Other factors to consider include whether there are effects from the known association between wrist ratio and CTS and assessing the benefits of neuromuscular ultrasound to diagnose CTS. Nocturnal paresthesias and paresthesias while holding onto an object were sensitive indicators of the presence of CTS but use of the Phalen and Hoffmann-Tinel signs has significant potential to be unreliable.

This article is the third in a series of four that explore the effects of age-related changes in impairments as defined by the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Fifth and Sixth Editions. Specifically, this article focuses on evaluation of disturbances of the nervous system, divided for discussion here into four parts—the central nervous system (CNS), the peripheral nervous system, vision, and hearing—and offers guidance in using the AMA Guides, Fifth and Sixth Editions, in a variety of specific disorders within each group. For example, the CNS discussions address disorders of consciousness and awareness; sleep and arousal disorders; alterations in metal status, cognition, and highest integrative function; aphasia or dysphagia; emotional or behavioral disorders resulting from CNS causation (fifth edition only); chronic pain; and others. One of the most challenging issues in evaluating peripheral neuropathy regards carpal tunnel syndrome, and rating physicians should provide references in their reports to justify their position. Rating visual problems usually requires attention to the medical records to document preinjury visual status. The AMA Guides, Fifth and Sixth Editions, do not use age-adjusted corrections in assessing age-related diminished hearing, but local jurisdictions and circumstances may apply apportionment. In apportioning impairment due to aging, the examiner must understand both the science and the specific legal processes involved.

Importance: Birth before 32 weeks’ gestation (very preterm [VPT]) and birth weight below 1500 g (very low birth weight [VLBW]) have been associated with lower cognitive performance in childhood. However, there are few investigations of the association of neonatal morbidities and maternal educational levels with the adult cognitive performance of individuals born VPT or VLBW (VPT/VLBW). Objective: To assess differences in adult IQ between VPT/VLBW and term-born individuals and to examine the association of adult IQ with cohort factors, neonatal morbidities, and maternal educational level among VPT/VLBW participants. Data Sources: Systematic review of published data from PubMed and meta-analysis of individual participant data (IPD) of cohorts from 2 consortia (Research on European Children and Adults Born Preterm [RECAP] and Adults Born Preterm International Collaboration [APIC]). Study Selection: The meta-analysis included prospective longitudinal cohort studies that assessed the full-scale IQ of adults born VPT or VLBW and respective control groups comprising term-born adults. Data Extraction And Synthesis: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for analyses of individual participant data and identified 8 studies that provided data from 2135 adults (1068 VPT/VLBW and 1067 term-born participants) born between 1978 and 1995. Meta-analyses of IPD were performed using a 1-stage approach, treating VPT birth or VLBW and cohort as random effects. Main Outcomes And Measures: Full-scale IQ scores were converted to z scores within each cohort using the combined SD of VPT/VLBW participants and a control group of term-born participants, with scores centered on the mean of the control group. Results: A total of 426 records were identified and screened. After exclusions, 13 studies were included in the aggregate meta-analysis. The IPD meta-analysis included 8 of the 9 RECAP and APIC cohorts with adult IQ data. The mean (SD) age among the 8 IPD cohorts was 24.6 (4.3) years, and 1163 participants (54.5%) were women. In unadjusted analyses, VPT/VLBW participants had mean adult IQ scores that were 0.78 SD (95% CI, −0.90 to −0.66 SD) lower than term-born participants, equivalent to a difference of 12 IQ points. Among VPT/VLBW participants, lower gestational age (score difference per week of gestation, 0.11; 95% CI, 0.07-0.14), lower birth weight z scores (score difference per 1.0 SD, 0.21; 95% CI, 0.14-0.28), the presence of neonatal bronchopulmonary dysplasia (score difference, −0.16; 95% CI, −0.30 to −0.02) or any grade of intraventricular hemorrhage (score difference, −0.19; 95% CI, −0.33 to −0.05), and lower maternal educational level (score difference, 0.26; 95% CI, 0.17-0.35) were all significantly associated with lower IQ scores in adulthood. Conclusions And Relevance: In this IPD meta-analysis, lower gestational age, lower weight for gestational age, neonatal morbidities, and lower maternal educational levels were all important risk factors associated with lower IQ among young adults born VPT or VLBW.

Importance Given that depression is treatable and some ocular diseases that cause visual loss are reversible, early identification and treatment of patients with visual impairment who are most at risk of depression may have an important influence on the well-being of these patients. Objective To conduct a meta-analysis on the prevalence of depression in patients with visual impairment who regularly visit eye clinics and low vision rehabilitation services. Data Sources MEDLINE (inception to June 7, 2020) and Embase (inception to June 7, 2020) were searched. Study Selection Studies that obtained data on the association between acquired visual impairment and depression among individuals aged 18 years or older were identified and included in this review. Exclusion criteria comprised inherited or congenital eye diseases, review studies, unpublished articles, abstracts, theses, dissertations, and book chapters. Four independent reviewers analyzed the results of the search and performed the selection and data extraction to ensure accuracy. Data Extraction and Synthesis Meta-analyses of prevalence were conducted using random-intercept logistic regression models. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Main Outcomes and Measures Proportion of depression. Results A total of 27 studies were included in this review, and all but 2 included patients older than 65 years. Among 6992 total patients (mean [SD] age, 76 [13.9] years; 4195 women [60%]) with visual impairment, in 1687 patients with depression, the median proportion of depression was 0.30 (range, 0.03-0.54). The random-effects pooled estimate was 0.25 (95% CI, 0.19-0.33) with high heterogeneity (95% predictive interval, 0.05-0.70). No patient characteristic, measured at the study level, influenced the prevalence of depression, except for the inclusion of patients with cognitive impairment (0.33; 95% CI, 0.28-0.38 in 14 studies vs 0.18; 95% CI, 0.11-0.30 in 13 studies that excluded this with major comorbidities;P = .008). The prevalence of depression was high both in clinic-based studies (in 6 studies, 0.34; 95% CI, 0.23-0.47) and in rehabilitation services (in 18 studies, 0.25; 95% CI, 0.18-0.33 vs other settings in 3 studies, 0.15; 95% CI, 0.05-0.38;P = .17), and did not vary by visual impairment severity of mild (in 8 studies, 0.24; 95% CI, 0.14-0.38), moderate (in 10 studies, 0.29; 95% CI, 0.21-0.39), and severe (in 5 studies, 0.29; 95% CI, 0.12-0.56;P = .51). Conclusions and Relevance The results of this meta-analysis suggest that depression in patients with visual impairment is a common problem that should be recognized and addressed by the health care professionals treating these patients.

IMPORTANCE: Although there were no differences in mean visual acuity (VA) over 24 weeks after vitrectomy with panretinal photocoagulation (PRP) vs aflibercept in a randomized clinical trial among eyes with vitreous hemorrhage due to proliferative diabetic retinopathy (PDR), post hoc analyses may influence treatment choices. OBJECTIVE: To compare exploratory outcomes between treatment groups that may affect treatment choices for patients with vitreous hemorrhage due to PDR. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of a randomized clinical trial conducted at 39 DRCR Retina Network sites included adults with vision loss due to PDR-related vitreous hemorrhage for whom vitrectomy was considered. Data were collected from November 2016 to January 2020. INTERVENTIONS: Random assignment to 4 monthly injections of aflibercept vs vitrectomy with PRP. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol-specific criteria. MAIN OUTCOMES AND MEASURES: Visual acuity area under the curve (adjusted for baseline VA) and clearance of vitreous hemorrhage. RESULTS: A total of 205 eyes were included in the analysis (115 male [56%] and 90 [44%] female participants; mean [SD] age, 57 [11] years). Among 89 eyes with a baseline VA of 20/32 to 20/160 (47 receiving aflibercept, including 4 [9%] that had undergone vitrectomy; 42 undergoing vitrectomy, including 3 [7%] that had received aflibercept), the adjusted mean difference in VA letter score over 24 weeks between the aflibercept and vitrectomy groups was −4.3 (95% CI, −10.6 to 1.9) compared with −16.7 (95% CI, −24.4 to −9.1) among 59 eyes with baseline VA worse than 20/800 (P = .02 for interaction; 26 in the aflibercept group, including 6 [23%] that had undergone vitrectomy; 33 in the vitrectomy group, including 8 [24%] that had received aflibercept). In the full cohort, the median time to clearance of the initial vitreous hemorrhage was 36 (interquartile range [IQR], 24-52) weeks in the aflibercept group vs 4 (IQR, 4-4) weeks in the vitrectomy group (difference, 32 [95% CI, 20-32] weeks; P

Importance Clinical data are lacking regarding the risk of viral transmission from individuals who have positive reverse-transcription–polymerase chain reaction (RT-PCR) SARS-CoV-2 test results after recovery from COVID-19. Objective To describe case characteristics, including viral dynamics and transmission of infection, for individuals who have clinically recovered from SARS-CoV-2 infection but continued to have positive test results following discontinuation of isolation precautions. Design, Setting, and Participants This retrospective cohort study used data collected from June 11, 2020, to October 19, 2020, as part of the National Basketball Association (NBA) closed campus occupational health program in Orlando, Florida, which required daily RT-PCR testing and ad hoc serological testing for SARS-CoV-2 IgG antibodies. Nearly 4000 NBA players, staff, and vendors participated in the NBA’s regular and postseason occupational health program in Orlando. Persistent positive cases were those who recovered from a documented SARS-CoV-2 infection, satisfied US Centers for Disease Control and Prevention criteria for discontinuation of isolation precautions, and had at least 1 postinfection positive RT-PCR test(s) result. Exposures Person-days of participation in indoor, unmasked activities that involved direct exposure between persistent positive cases and noninfected individuals. Main Outcomes and Measures Transmission of SARS-CoV-2 following interaction with persistent positive individuals, as measured by the number of new COVID-19 cases in the Orlando campus program. Results Among 3648 individuals who participated, 36 (1%) were persistent positive cases, most of whom were younger than 30 years (24 [67%]) and male (34 [94%]). Antibodies were detected in 33 individuals (91.7%); all remained asymptomatic following the index persistent positive RT-PCR result. Cycle threshold values for persistent positive RT-PCR test results were typically above the Roche cobas SARS-CoV-2 limit of detection. Cases were monitored for up to 100 days (mean [SD], 51 [23.9] days), during which there were at least 1480 person-days of direct exposure activities, with no transmission events or secondary infections of SARS-CoV-2 detected (0 new cases). Conclusions and Relevance In this retrospective cohort study of the 2020 NBA closed campus occupational health program, recovered individuals who continued to test positive for SARS-CoV-2 following discontinuation of isolation were not infectious to others. These findings support time-based US Centers of Disease Control and Prevention recommendations for ending isolation.

This population epidemiology study characterizes trends in the prevalence of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among international entrants testing positive for SARS-CoV-2 at Chinese border checkpoints between mid-April and mid-October 2020.

This cross-sectional study assesses trends in suicide-related internet search rates in the early stages of the COVID-19 pandemic in the US.

Key Points Question In a large county health care system with access to inpatient and outpatient testing, is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection associated with pregnancy outcomes, maternal illness severity, placental pathology, and neonatal infections? Findings In this cohort study of 252 SARS-CoV-2–positive and 3122 negative pregnant women tested in outpatient and inpatient settings at a large county medical center, adverse pregnancy outcomes were similar, and neonatal infection occurred in 3% of infants, predominantly among infants born to asymptomatic or mildly symptomatic women. Placental abnormalities were not associated with disease severity, and the rate of hospitalization was similar to rates among nonpregnant women. Meaning These findings suggest that SARS-CoV-2 infection in pregnancy is not associated with adverse pregnancy outcomes., This cohort study evaluates the adverse outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among pregnant women and describes clinical management, disease progression, hospital admission, placental abnormalities, and neonatal outcomes., Importance Published data suggest that there are increased hospitalizations, placental abnormalities, and rare neonatal transmission among pregnant women with coronavirus disease 2019 (COVID-19). Objectives To evaluate adverse outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy and to describe clinical management, disease progression, hospital admission, placental abnormalities, and neonatal outcomes. Design, Setting, and Participants This observational cohort study of maternal and neonatal outcomes among delivered women with and without SARS-CoV-2 during pregnancy was conducted from March 18 through August 22, 2020, at Parkland Health and Hospital System (Dallas, Texas), a high-volume prenatal clinic system and public maternity hospital with widespread access to SARS-CoV-2 testing in outpatient, emergency department, and inpatient settings. Women were included if they were tested for SARS-CoV-2 during pregnancy and delivered. For placental analysis, the pathologist was blinded to illness severity. Exposures SARS-CoV-2 infection during pregnancy. Main Outcomes and Measures The primary outcome was a composite of preterm birth, preeclampsia with severe features, or cesarean delivery for abnormal fetal heart rate among women delivered after 20 weeks of gestation. Maternal illness severity, neonatal infection, and placental abnormalities were described. Results From March 18 through August 22, 2020, 3374 pregnant women (mean [SD] age, 27.6 [6] years) tested for SARS-CoV-2 were delivered, including 252 who tested positive for SARS-CoV-2 and 3122 who tested negative. The cohort included 2520 Hispanic (75%), 619 Black (18%), and 125 White (4%) women. There were no differences in age, parity, body mass index, or diabetes among women with or without SARS-CoV-2. SARS-CoV-2 positivity was more common among Hispanic women (230 [91%] positive vs 2290 [73%] negative; difference, 17.9%; 95% CI, 12.3%-23.5%; P

IMPORTANCE: It remains unknown whether in an asymptomatic community-based cohort magnetic resonance imaging (MRI) measures of plaque characteristics are independently associated with incident cardiovascular disease (CVD) events when adjusted for carotid artery (CA) wall thickness, a measure of plaque burden. OBJECTIVE: To assess associations of CA MRI plaque characteristics with incident CVD events. DESIGN, SETTING, AND PARTICIPANTS: The Atherosclerosis Risk in Communities (ARIC) study is a prospective epidemiologic study of the incidence of CVD in 15 792 adults of which 2066 women and men were enrolled in the ARIC Carotid MRI substudy. ARIC participants were enrolled from 1987 to 1989, and the substudy was conducted between January 2004 and December 2005. Analysis began January 2017 and ended August 2020. EXPOSURES: Incident CVD events during a median (interquartile range [IQR]) follow-up time of 10.5 (8.1-10.9) years were assessed. MAIN OUTCOMES AND MEASURES: Proportional hazards Cox analyses were performed to ascertain associations between MRI variables of CA plaque burden and plaque characteristics. RESULTS: Of 15 792 ARIC participants, 2066 were enrolled in the substudy, of whom 1256 (701 women [55.8%]) had complete data and were eligible for incident CVD analyses. Carotid artery plaques in participants with incident CVD events (172 [13.7%]) compared with those without (1084 [86.3%]) had a higher normalized wall index (median [IQR], 0.48 [0.36-0.62] vs 0.43 [0.34-0.55]; P = .001), maximum CA wall thickness (median [IQR], 2.22 [1.37-3.52] mm vs 1.96 [1.29-2.85] mm; P = .01), maximum CA stenosis (median [IQR], 5% [0%-22%] vs 0% [0%-13%]; P

This case series describes the appearance of enanthem (oral cavity lesions) in patients with COVID-19.

This cohort study evaluates the incidence of nosocomial coronavirus disease 2019 (COVID-19) among patients admitted to a US medical center in the context of a comprehensive and progressive infection control program., Key Points Question What is the incidence of hospital-acquired coronavirus disease 2019 (COVID-19) at a large US academic medical center? Findings In this cohort study of 9149 patients admitted to a large US academic medical center over a 12-week period, 697 were diagnosed with COVID-19. In the context of a comprehensive and progressive infection control program, only 2 hospital-acquired cases were detected: 1 patient was likely infected by a presymptomatic spouse before visitor restrictions were implemented, and 1 patient developed symptoms 4 days after a 16-day hospitalization but without known exposures in the hospital. Meaning These findings suggest that overall risk of hospital-acquired COVID-19 was low and that rigorous infection control measures may be associated with minimized risk., Importance Some patients are avoiding essential care for fear of contracting coronavirus disease 2019 (COVID-19) in hospitals. There are few data, however, on the risk of acquiring COVID-19 in US hospitals. Objective To assess the incidence of COVID-19 among patients hospitalized at a large US academic medical center in the 12 weeks after the first inpatient case was identified. Design, Setting, and Participants This cohort study included all patients admitted to Brigham and Women’s Hospital (Boston, Massachusetts) between March 7 and May 30, 2020. Follow-up occurred through June 17, 2020. Medical records for all patients who first tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse-transcription polymerase chain reaction (RT-PCR) on hospital day 3 or later or within 14 days of discharge were reviewed. Exposures A comprehensive infection control program was implemented that included dedicated COVID-19 units with airborne infection isolation rooms, personal protective equipment in accordance with US Centers for Disease Control and Prevention recommendations, personal protective equipment donning and doffing monitors, universal masking, restriction of visitors, and liberal RT-PCR testing of symptomatic and asymptomatic patients. Main Outcomes and Measures Whether infection was community or hospital acquired based on timing of tests, clinical course, and exposures. Results Over the 12-week period, 9149 patients (mean [SD] age, 46.1 [26.4] years; median [IQR] age, 51 years [30-67 years]; 5243 female [57.3%]) were admitted to the hospital, for whom 7394 SARS-CoV-2 RT-PCR tests were performed; 697 COVID-19 cases were confirmed, translating into 8656 days of COVID-19–related care. Twelve of the 697 hospitalized patients with COVID-19 (1.7%) first tested positive on hospital day 3 or later (median, 4 days; range, 3-15 days). Of these, only 1 case was deemed to be hospital acquired, most likely from a presymptomatic spouse who was visiting daily and diagnosed with COVID-19 before visitor restrictions and masking were implemented. Among 8370 patients with non–COVID-19–related hospitalizations discharged through June 17, 11 (0.1%) tested positive within 14 days (median time to diagnosis, 6 days; range, 1-14 days). Only 1 case was deemed likely to be hospital acquired, albeit with no known exposures. Conclusions and Relevance In this cohort study of patients in a large academic medical center with rigorous infection control measures, nosocomial COVID-19 was rare during the height of the pandemic in the region. These findings may inform practices in other institutions and provide reassurance to patients concerned about contracting COVID-19 in hospitals.

This cohort study compares the clinical features of coronavirus disease 2019 (COVID-19) with those of influenza A and B in US children., Key Points Question What are the similarities and differences in clinical features between coronavirus disease 2019 (COVID-19) and seasonal influenza in US children? Findings In this cohort study of 315 children with COVID-19 and 1402 children with seasonal influenza, there were no statistically significant differences in the rates of hospitalization, admission to the intensive care unit, and mechanical ventilator use between the 2 groups. More patients with COVID-19 than with seasonal influenza reported fever, diarrhea or vomiting, headache, body ache, or chest pain at the time of diagnosis. Meaning The findings suggest that prevention of both COVID-19 and seasonal influenza in US children is prudent and urgent for the well-being of this population., Importance Compared with seasonal influenza, the clinical features and epidemiologic characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus 2019 (COVID-19) in US children remain largely unknown. Objective To describe the similarities and differences in clinical features between COVID-19 and seasonal influenza in US children. Design, Setting, and Participants This retrospective cohort study included children who were diagnosed with laboratory-confirmed COVID-19 between March 25 and May 15, 2020, and children diagnosed with seasonal influenza between October 1, 2019, and June 6, 2020, at Children’s National Hospital in the District of Columbia. Exposures COVID-19 or influenza A or B. Main Outcomes and Measures Rates of hospitalization, admission to the intensive care unit, and mechanical ventilator use and the association between underlying medical conditions, clinical symptoms, and COVID-19 vs seasonal influenza. Results The study included 315 patients diagnosed with COVID-19 (164 [52%] male; median age, 8.3 years [range, 0.03-35.6 years]) and 1402 patients diagnosed with seasonal influenza (743 [53%] male; median age, 3.9 years [range, 0.04-40.4 years]). Patients with COVID-19 and those with seasonal influenza had a similar hospitalization rate (54 [17%] vs 291 [21%], P = .15), intensive care unit admission rate (18 [6%] vs 98 [7%], P = .42), and use of mechanical ventilators (10 [3%] vs 27 [2%], P = .17). More patients hospitalized with COVID-19 than with seasonal influenza reported fever (41 [76%] vs 159 [55%], P = .005), diarrhea or vomiting (14 [26%] vs 36 [12%], P = .01), headache (6 [11%] vs 9 [3%], P = .01), body ache or myalgia (12 [22%] vs 20 [7%], P = .001), and chest pain (6 [11%] vs 9 [3%], P = .01). Differences between patients hospitalized with COVID-19 vs influenza who reported cough (24 [48%] vs 90 [31%], P = .05) and shortness of breath (16 [30%] vs 59 [20%], P = .13) were not statistically significant. Conclusions and Relevance In this cohort study of US children with COVID-19 or seasonal influenza, there was no difference in hospitalization rates, intensive care unit admission rates, and mechanical ventilator use between the 2 groups. More patients hospitalized with COVID-19 than with seasonal influenza reported clinical symptoms at the time of diagnosis.

This cohort study investigates the depression and anxiety of children in Wuhan and Huangshi, Hubei province, China, during the coronavirus disease 2019 lockdown.

This case series describes COVID-19 symptoms persisting a mean of 60 days after onset among Italian patients previously discharged from COVID-19 hospitalization.

Importance The influence on the psychology and ocular surface of ophthalmologists and ophthalmic nurses in Wuhan, China, during the coronavirus disease 2019 (COVID-19) pandemic is not yet fully understood. Objective To characterize mental state and ocular surface state of ophthalmologists and ophthalmic nurses in Wuhan, China, and similar areas during the COVID-19 outbreak. Design, Setting, and Participants This survey study assessed ophthalmologists and ophthalmic nurses in Wuhan, China, and Jiangxi, China, a province approximately 300 km south of Wuhan. The Hospital Anxiety and Depression Scale, the Van Dream Anxiety Scale, and the Ocular Surface Disease Index were used to conduct questionnaire surveys via a messaging and social media app. Main Outcomes and Measures Mean scores from the Hospital Anxiety and Depression Scale (0-10 points), the Van Dream Anxiety Scale (0-100 points), and the Ocular Surface Disease Index (0-100 points). Results Of 126 individuals, there were 42 ophthalmologists (33.3%) and 21 ophthalmic nurses (16.7%) from Wuhan and 42 ophthalmologists (33.3%) and 21 nurses (16.7%) from Jiangxi. The mean (SD) age of ophthalmologists was 36.1 (7.6) years in Wuhan and 41.2 (8.8) years in Jiangxi. For ophthalmic nurses, the mean (SD) age was 35.2 (7.4) years in Wuhan and 33.4 (7.9) years in Jiangxi. The response rate for ophthalmologists was 90.3% (84 of 93) and for nurses was 91.3% (42 of 46). The participation rate of ophthalmologists and nurses in Wuhan was 0.06% (42 of 70 000) and 0.07% (21 of 30 000), respectively; the participation rate in Jiangxi was 0.06% (42 of 70 000; 21 of 35 000) for both groups. In Wuhan, the mean (SD) Hospital Anxiety and Depression Scale (anxiety and depression were counted as separate scores), Van Dream Anxiety Scale, and the Ocular Surface Disease Index scores were 6.90 (2.30), 7.38 (2.19), 24.52 (5.86), and 43.90 (3.74), respectively, in ophthalmologists and 8.67 (3.04), 9.38 (2.64), 21.48 (6.15), and 40.05 (6.67), respectively, in ophthalmic nurses. In Jiangxi, these scores were 5.67 (2.89), 4.90 (3.15), 12.76 (7.27), and 38.79 (7.78), respectively, in ophthalmologists and 4.67 (3.20), 4.33 (3.23), 10.10 (7.62), and 41.52 (5.92), respectively, in ophthalmic nurses. The difference (95% CI) between the 2 regions for these scores in ophthalmologists was 2.48 (95% CI, 1.30-3.65), 11.76 (95% CI, 8.90-14.63), 5.12 (95% CI, 2.45-7.79), and 5.12 (95% CI, 2.47-7.77), respectively, and in ophthalmic nurses was 4.16 (95% CI, 2.05-5.95), 5.05 (95% CI, 3.21-6.89), 11.38 (95% CI, 7.06-15.70), and −1.48 (95% CI, −5.41 to 2.25), respectively. Conclusions and Relevance These findings suggest that ophthalmologists and ophthalmic nurses in Wuhan experienced more anxiety and depression and reported greater ocular surface abnormalities than counterparts outside of Wuhan, but the wide CIs preclude concluding confidently that there were differences.

Key Points Question What is the clinical presentation to emergency medical services among persons with coronavirus disease 2019 (COVID-19)? Findings This cohort study of 124 patients with COVID-19 revealed that most patients with COVID-19 presenting to emergency medical services were older and had multiple chronic health conditions. Initial concern, symptoms, and examination findings were heterogeneous and not consistently characterized as febrile respiratory illness. Meaning The findings of this study suggest that the conventional description of febrile respiratory illness may not adequately identify COVID-19 in the prehospital emergency setting., This cohort study describes patient characteristics and prehospital presentation of patients with coronavirus disease 2019 (COVID-19) cared for by emergency medical services (EMS) in King County, Washington., Importance The ability to identify patients with coronavirus disease 2019 (COVID-19) in the prehospital emergency setting could inform strategies for infection control and use of personal protective equipment. However, little is known about the presentation of patients with COVID-19 requiring emergency care, particularly those who used 911 emergency medical services (EMS). Objective To describe patient characteristics and prehospital presentation of patients with COVID-19 cared for by EMS. Design, Setting, and Participants This retrospective cohort study included 124 patients who required 911 EMS care for COVID-19 in King County, Washington, a large metropolitan region covering 2300 square miles with 2.2 million residents in urban, suburban, and rural areas, between February 1, 2020, and March 18, 2020. Exposures COVID-19 was diagnosed by reverse transcription–polymerase chain reaction detection of severe acute respiratory syndrome coronavirus 2 from nasopharyngeal swabs. Test results were available a median (interquartile range) of 5 (3-9) days after the EMS encounter. Main Outcomes and Measures Prevalence of clinical characteristics, symptoms, examination signs, and EMS impression and care. Results Of the 775 confirmed COVID-19 cases in King County, EMS responded to 124 (16.0%), with a total of 147 unique 911 encounters. The mean (SD) age was 75.7 (13.2) years, 66 patients (53.2%) were women, 47 patients (37.9%) had 3 or more chronic health conditions, and 57 patients (46.0%) resided in a long-term care facility. Based on EMS evaluation, 43 of 147 encounters (29.3%) had no symptoms of fever, cough, or shortness of breath. Based on individual examination findings, fever, tachypnea, or hypoxia were only present in a limited portion of cases, as follows: 43 of 84 encounters (51.2%), 42 of 131 (32.1%), and 60 of 112 (53.6%), respectively. Advanced care was typically not required, although in 24 encounters (16.3%), patients received care associated with aerosol-generating procedures. As of June 1, 2020, mortality among the study cohort was 52.4% (65 patients). Conclusions and Relevance The findings of this cohort study suggest that screening based on conventional COVID-19 symptoms or corresponding examination findings of febrile respiratory illness may not possess the necessary sensitivity for early diagnostic suspicion, at least in the prehospital emergency setting. The findings have potential implications for early identification of COVID-19 and effective strategies to mitigate infectious risk during emergency care.

This study used national survey data to compare the prevalence symptoms of psychological distress and loneliness among US adults during the coronavirus disease 2019 (COVID-19) pandemic in April 2020 vs those reported in the National Health Interview Survey in 2018.

Key Points Question What are the immunologic features of pediatric patients with pneumonia caused by coronavirus disease 2019 (COVID-19)? Findings In this single-center case series involving 157 pediatric patients with COVID-19, systemic inflammation rarely occurred. Patients with moderate disease had higher interleukin 10 levels and lower neutrophil levels than patients with mild disease. Meaning The results of this study suggest that dysregulation of immune response may be involved in the pathologic process of COVID-19; gaining a deeper understanding of the role of neutrophils, CD4+ T cells, and B cells in the pathogenesis of severe acute respiratory syndrome coronavirus 2 infection could be important for the clinical management of COVID-19., This case series delineates and compares the immunologic features of mild and moderate coronavirus disease 2019 (COVID-19) in pediatric patients., Importance The epidemiologic and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) have been reported, but information on immune features associated with disease severity is scarce. Objective To delineate and compare the immunologic features of mild and moderate COVID-19 in pediatric patients. Design, Setting, and Participants This single-center case series included 157 pediatric patients admitted to Wuhan Children’s Hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were collected from January 25 to April 18, 2020. Exposures Documented SARS-CoV-2 infection. Main Outcomes and Measures Clinical and immunologic characteristics were collected and analyzed. Outcomes were observed until April 18, 2020. Results Of the 157 pediatric patients with COVID-19, 60 (38.2%) had mild clinical type with pneumonia, 88 (56.1%) had moderate cases, 6 (3.8%) had severe cases, and 3 (1.9%) were critically ill. The 148 children with mild or moderate disease had a median (interquartile range [IQR]) age of 84 (18-123) months, and 88 (59.5%) were girls. The most common laboratory abnormalities were increased levels of alanine aminotransferase (ALT) (median [IQR], 16.0 [12.0-26.0] U/L), aspartate aminotransferase (AST) (median [IQR], 30.0 [23.0-41.8] U/L), creatine kinase MB (CK-MB) activity (median [IQR], 24.0 [18.0-34.0] U/L), and lactate dehydrogenase (LDH) (median [IQR], 243.0 [203.0-297.0] U/L), which are associated with liver and myocardial injury. Compared with mild cases, levels of inflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ were unchanged, whereas the level of immune suppressive interleukin 10 was markedly increased in moderate cases compared with mild cases (median [IQR], 3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = .048). There was no statistically significant difference in absolute number of lymphocytes (including T cells and B cells) between mild and moderate cases, but moderate cases were associated with a decrease in neutrophil levels compared with mild cases (median [IQR], 2310/μL [1680/μL-3510/μL] vs 3120/μL [2040/μL-4170/μL]; P = .01). Immunoglobin G and the neutrophil to lymphocyte ratio were negatively associated with biochemical indices related to liver and myocardial injury (immunoglobulin G, ALT: r, −0.3579; AST: r, −0.5280; CK-MB activity: r, −0.4786; LDH: r, −0.4984; and neutrophil to lymphocyte ratio, ALT: r, −0.1893; AST: r, −0.3912; CK-MB activity: r, −0.3428; LDH: r, −0.3234), while counts of lymphocytes, CD4+ T cells, and interleukin 10 showed positive associations (lymphocytes, ALT: r, 0.2055; AST: r, 0.3615; CK-MB activity: r, 0.338; LDH: r, 0.3309; CD4+ T cells, AST: r, 0.4701; CK-MB activity: r, 0.4151; LDH: r, 0.4418; interleukin 10, ALT: r, 0.2595; AST: r, 0.3386; CK-MB activity: r, 0.3948; LDH: r, 0.3794). Conclusions and Relevance In this case series, systemic inflammation rarely occurred in pediatric patients with COVID-19, in contrast with the lymphopenia and aggravated inflammatory responses frequently observed in adults with COVID-19. Gaining a deeper understanding of the role of neutrophils, CD4+ T cells, and B cells in the pathogenesis of SARS-CoV-2 infection could be important for the clinical management of COVID-19.

This cohort study assesses anxiety, depression, mood, and fear of workplace violence in a cohort of young physicians in China before and during the coronavirus disease 2019 outbreak.

Importance The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations. Objective To study the neurologic manifestations of patients with COVID-19. Design, Setting, and Participants This is a retrospective, observational case series. Data were collected from January 16, 2020, to February 19, 2020, at 3 designated special care centers for COVID-19 (Main District, West Branch, and Tumor Center) of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. The study included 214 consecutive hospitalized patients with laboratory-confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 infection. Main Outcomes and Measures Clinical data were extracted from electronic medical records, and data of all neurologic symptoms were checked by 2 trained neurologists. Neurologic manifestations fell into 3 categories: central nervous system manifestations (dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system manifestations (taste impairment, smell impairment, vision impairment, and nerve pain), and skeletal muscular injury manifestations. Results Of 214 patients (mean [SD] age, 52.7 [15.5] years; 87 men [40.7%]) with COVID-19, 126 patients (58.9%) had nonsevere infection and 88 patients (41.1%) had severe infection according to their respiratory status. Overall, 78 patients (36.4%) had neurologic manifestations. Compared with patients with nonsevere infection, patients with severe infection were older, had more underlying disorders, especially hypertension, and showed fewer typical symptoms of COVID-19, such as fever and cough. Patients with more severe infection had neurologic manifestations, such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]), and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]). Conclusions and Relevance Patients with COVID-19 commonly have neurologic manifestations. During the epidemic period of COVID-19, when seeing patients with neurologic manifestations, clinicians should suspect severe acute respiratory syndrome coronavirus 2 infection as a differential diagnosis to avoid delayed diagnosis or misdiagnosis and lose the chance to treat and prevent further transmission.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) was identified as a new coronavirus causing pneumonia and acute respiratory distress syndrome. It has become a pandemic, spreading particularly quickly across Europe and the US. Most deaths are related to severe acute respiratory distress syndrome, but other organ failures, such as acute kidney failure and acute cardiac injury, seem also related to the disease.1 Inflammatory response is highly increased in coronavirus disease 2019 (COVID-19) infection, and inflammation is known to favor thrombosis. High dimerized plasmin fragment D (D-dimer) levels and procoagulant changes in coagulation pathways were reported among patients with severe COVID-19.2,3 An elevated rate of venous and arterial thrombotic events associated with COVID-19 infection has also been reported.4,5 This case series reports a systematic assessment of deep vein thrombosis among patients in an intensive care unit (ICU) in France with severe COVID-19.

This case series examines clinical characteristics of patients with asymptomatic vs symptomatic coronavirus disease 2019 in Wuhan, China.

Importance While the outbreak of coronavirus disease 2019 (COVID-19) has resulted in more than 100 000 infected individuals in China and worldwide, there are few reports on the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with ocular abnormalities. Understanding ocular manifestations of patients with COVID-19 by ophthalmologists and others may facilitate the diagnosis and prevention of transmission of the disease. Objective To investigate ocular manifestations and viral prevalence in the conjunctiva of patients with COVID-19. Design, Setting, and Participants In this case series, patients with COVID-19 treated from February 9 to 15, 2020, at a hospital center in Hubei province, China, were retrospectively reviewed for ocular manifestations. During the period of treatment, the ocular signs and symptoms as well as results of blood tests and reverse transcriptase–polymerase chain reaction (RT-PCR) from nasopharyngeal and conjunctival swabs for SARS-CoV-2 were noted and analyzed. Main Outcomes and Measures Ocular signs and symptoms as well as results of blood tests and RT-PCR for SARS-CoV-2. Results Of the 38 included patients with clinically confirmed COVID-19, 25 (65.8%) were male, and the mean (SD) age was 65.8 (16.6) years. Among them, 28 patients (73.7%) had positive findings for COVID-19 on RT-PCR from nasopharyngeal swabs, and of these, 2 patients (5.2%) yielded positive findings for SARS-CoV-2 in their conjunctival as well as nasopharyngeal specimens. A total of 12 of 38 patients (31.6%; 95% CI, 17.5-48.7) had ocular manifestations consistent with conjunctivitis, including conjunctival hyperemia, chemosis, epiphora, or increased secretions. By univariate analysis, patients with ocular symptoms were more likely to have higher white blood cell and neutrophil counts and higher levels of procalcitonin, C-reactive protein, and lactate dehydrogenase than patients without ocular symptoms. In addition, 11 of 12 patients with ocular abnormalities (91.7%; 95% CI, 61.5-99.8) had positive results for SARS-CoV-2 on RT-PCR from nasopharyngeal swabs. Of these, 2 (16.7%) had positive results for SARS-CoV-2 on RT-PCR from both conjunctival and nasopharyngeal swabs. Conclusions and Relevance In this study, one-third of patients with COVID-19 had ocular abnormalities, which frequently occurred in patients with more severe COVID-19. Although there is a low prevalence of SARS-CoV-2 in tears, it is possible to transmit via the eyes.

Importance Recent accounts suggest that delusions and hallucinations may result from alterations in how prior knowledge is integrated with new information, but experimental evidence supporting this idea has been complex and inconsistent. Evidence from a simpler perceptual task would make clear whether psychotic symptoms are associated with overreliance on prior information and impaired updating. Objective To investigate whether individuals with schizophrenia or schizoaffective disorder (PSZ) and healthy control individuals (HCs) differ in the ability to update their beliefs based on evidence in a relatively simple perceptual paradigm. Design, setting, and participants This case-control study included individuals who met DSM-IV criteria for PSZ and matched HC participants in 2 independent samples. The PSZ group was recruited from the Maryland Psychiatric Research Center, Yale University, and community clinics, and the HC group was recruited from the community. To test perceptual updating, a random dot kinematogram paradigm was implemented in which dots moving coherently in a single direction were mixed with randomly moving dots. On 50% of trials, the direction of coherent motion changed by 90° midway through the trial. Participants were asked to report the direction perceived at the end of the trial. The Peters Delusions Inventory and Brief Psychiatric Rating Scale (BPRS) were used to quantify the severity of positive symptoms. Data were collected from September 2018 to March 2020 and were analyzed from approximately March 2020 to March 2021. Main outcomes and measures Critical measures included the proportion of responses centered around the initial direction vs the subsequent changed direction and the overall precision of motion perception and reaction times. Results A total of 48 participants were included in the PSZ group (31 [65%] male; mean [SD] age, 36.56 [9.76] years) and 36 in the HC group (22 [61%] male; mean [SD] age, 35.67 [10.74] years) in the original sample. An independent replication sample included 42 participants in the PSZ group (29 [69%] male; mean [SD] age, 33.98 [11.03] years) and 34 in the HC group (20 [59%] male; mean [SD] age, 34.29 [10.44] years). In line with previous research, patients with PSZ were less precise and had slower reaction times overall. The key finding was that patients with PSZ were significantly more likely (original sample: mean, 27.88 [95% CI, 24.19-31.57]; replication sample: mean, 26.70 [95% CI, 23.53-29.87]) than HC participants (original sample: mean, 18.86 [95% CI, 16.56-21.16]; replication sample: mean, 15.67 [95% CI, 12.61-18.73]) to report the initial motion direction rather than the final one. Moreover, the tendency to report the direction of initial motion correlated with the degree of conviction on the Peters Delusions Inventory (original sample: r = 0.32 [P = .05]; replication sample: r = 0.30 [P = .05]) and the Brief Psychiatric Rating Scale Reality Distortion score (original sample: r = 0.55 [P = .001]; replication sample: r = 0.35 [P = .03]) and severity of hallucinations (original sample: r = 0.39 [P = .02]; replication sample: r = 0.30 [P = .05]). Conclusions and relevance The findings of this case-control study suggest that the severity of psychotic symptoms is associated with a tendency to overweight initial information over incoming sensory evidence. These results are consistent with predictive coding accounts of the origins of positive symptoms and suggest that deficits in very elementary perceptual updating may be a critical mechanism in psychosis.

Importance There exists a paucity of literature that summarizes the effective management of cutaneous immune-related adverse events (cirAEs) in patients with cancer who are receiving immune checkpoint inhibitors (ICIs). Most published articles are small case series from a single institution. To our knowledge, the spectrum of possible treatments has not been systematically reviewed to highlight the breadth of options when caring for patients with cirAEs. Objective To further characterize the development of subtypes of cirAEs in patients with cancer treated with ICIs and provide recommendations on optimal treatment regimens based on the current literature. Evidence review A search was performed in PubMed, Embase European, Web of Science, and Google Scholar on June 26, 2020, according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, limited to the years 2010 to 2020. Articles that met predetermined inclusion criteria (published between January 1, 2010, and June 1, 2020; written in the English language; and original articles, brief reports, case reports, and research letters that reported primarily on cirAE management) were selected, and data were abstracted. Articles that met the scope of the review were also added from reference lists. When possible, the results of studies that addressed a similar question were combined quantitatively. Findings In total, 138 studies (87 from the aforementioned literature search and 51 additional studies pulled from the reference lists of included articles) were included that reported on 879 cirAEs. The subtypes of cirAEs included maculopapular, pruritus, lichenoid, immunobullous, psoriasiform, granulomatous, erythema multiforme or Stevens Johnson Syndrome, drug rash with eosinophilia and systemic symptoms, connective tissue disease, hair, oral, and miscellaneous. Treatments for cirAEs included a combination of topical corticosteroids, systemic corticosteroids, steroid-sparing agents, and discontinuation or cessation of immunotherapy. Conclusions and relevance This systematic review found that treatment with ICIs was associated with many types of skin toxic effects, each with unique treatment options beyond current published guidelines. Further research into key differences between subtypes is critical to improve the care provided to patients with cancer.

Importance Systemic corticosteroids are commonly used in treating severe COVID-19. However, the role of inhaled corticosteroids in the treatment of patients with mild to moderate disease is less clear. Objective To determine the efficacy of the inhaled steroid ciclesonide in reducing the time to alleviation of all COVID-19-related symptoms among nonhospitalized participants with symptomatic COVID-19 infection. Design, setting, and participants This phase 3, multicenter, double-blind, randomized clinical trial was conducted at 10 centers throughout the US and assessed the safety and efficacy of a ciclesonide metered-dose inhaler (MDI) for treating nonhospitalized participants with symptomatic COVID-19 infection who were screened from June 11, 2020, to November 3, 2020. Interventions Participants were randomly assigned to receive ciclesonide MDI, 160 μg per actuation, for a total of 2 actuations twice a day (total daily dose, 640 μg) or placebo for 30 days. Main outcomes and measures The primary end point was time to alleviation of all COVID-19-related symptoms (cough, dyspnea, chills, feeling feverish, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste or smell) by day 30. Secondary end points included subsequent emergency department visits or hospital admissions for reasons attributable to COVID-19. Results A total of 413 participants were screened and 400 (96.9%) were enrolled and randomized (197 [49.3%] in the ciclesonide arm and 203 [50.7%] in the placebo arm; mean [SD] age, 43.3 [16.9] years; 221 [55.3%] female; 2 [0.5%] Asian, 47 [11.8%] Black or African American, 3 [0.8%] Native Hawaiian or other Pacific Islander, 345 [86.3%] White, and 1 multiracial individuals [0.3%]; 172 Hispanic or Latino individuals [43.0%]). The median time to alleviation of all COVID-19-related symptoms was 19.0 days (95% CI, 14.0-21.0) in the ciclesonide arm and 19.0 days (95% CI, 16.0-23.0) in the placebo arm. There was no difference in resolution of all symptoms by day 30 (odds ratio, 1.28; 95% CI, 0.84-1.97). Participants who were treated with ciclesonide had fewer subsequent emergency department visits or hospital admissions for reasons related to COVID-19 (odds ratio, 0.18; 95% CI, 0.04-0.85). No participants died during the study. Conclusions and relevance The results of this randomized clinical trial demonstrated that ciclesonide did not achieve the primary efficacy end point of reduced time to alleviation of all COVID-19-related symptoms. Trial registration ClinicalTrials.gov Identifier: NCT04377711.

Importance Chronic back pain (CBP) is a leading cause of disability, and treatment is often ineffective. Approximately 85% of cases are primary CBP, for which peripheral etiology cannot be identified, and maintenance factors include fear, avoidance, and beliefs that pain indicates injury. Objective To test whether a psychological treatment (pain reprocessing therapy [PRT]) aiming to shift patients' beliefs about the causes and threat value of pain provides substantial and durable pain relief from primary CBP and to investigate treatment mechanisms. Design, setting, and participants This randomized clinical trial with longitudinal functional magnetic resonance imaging (fMRI) and 1-year follow-up assessment was conducted in a university research setting from November 2017 to August 2018, with 1-year follow-up completed by November 2019. Clinical and fMRI data were analyzed from January 2019 to August 2020. The study compared PRT with an open-label placebo treatment and with usual care in a community sample. Interventions Participants randomized to PRT participated in 1 telehealth session with a physician and 8 psychological treatment sessions over 4 weeks. Treatment aimed to help patients reconceptualize their pain as due to nondangerous brain activity rather than peripheral tissue injury, using a combination of cognitive, somatic, and exposure-based techniques. Participants randomized to placebo received an open-label subcutaneous saline injection in the back; participants randomized to usual care continued their routine, ongoing care. Main outcomes and measures One-week mean back pain intensity score (0 to 10) at posttreatment, pain beliefs, and fMRI measures of evoked pain and resting connectivity. Results At baseline, 151 adults (54% female; mean [SD] age, 41.1 [15.6] years) reported mean (SD) pain of low to moderate severity (mean [SD] pain intensity, 4.10 [1.26] of 10; mean [SD] disability, 23.34 [10.12] of 100) and mean (SD) pain duration of 10.0 (8.9) years. Large group differences in pain were observed at posttreatment, with a mean (SD) pain score of 1.18 (1.24) in the PRT group, 2.84 (1.64) in the placebo group, and 3.13 (1.45) in the usual care group. Hedges g was -1.14 for PRT vs placebo and -1.74 for PRT vs usual care (P Conclusions and relevance Psychological treatment centered on changing patients' beliefs about the causes and threat value of pain may provide substantial and durable pain relief for people with CBP. Trial registration ClinicalTrials.gov Identifier: NCT03294148.

Importance Older adults with insomnia have a high risk of incident and recurrent depression. Depression prevention is urgently needed, and such efforts have been neglected for older adults. Objective To examine whether treatment of insomnia disorder with cognitive behavioral therapy for insomnia (CBT-I) compared with an active comparator condition, sleep education therapy (SET), prevents major depressive disorder in older adults. Design, setting, and participants This assessor-blinded, parallel-group, single-site randomized clinical trial assessed a community-based sample of 431 people and enrolled 291 adults 60 years or older with insomnia disorder who had no major depression or major health events in past year. Study recruitment was performed from July 1, 2012, to April 30, 2015. The trial protocol was modified to extend follow-up from 24 to 36 months, with follow-up completion in July 2018. Data analysis was performed from March 1, 2019, to March 30, 2020. Interventions Participants were randomized to 2 months of CBT-I (n = 156) or SET (n = 135). Main outcomes and measures The primary outcome was time to incident major depressive disorder as diagnosed by interview and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria. Secondary outcome was sustained remission of insomnia disorder before depression event or duration of follow-up. Results Among 291 randomized participants (mean [SD] age, 70.1 [6.7] years; 168 [57.7%] female; 7 [2.4%] Asian, 32 [11.0%] Black, 3 [1.0%] Pacific Islander, 241 [82.8%] White, 6 [2.1%] multiracial, and 2 [0.7%] unknown), 156 were randomized to CBT-I and 135 to SET. A total of 140 participants (89.7%) completed CBT-I and 130 (96.3%) participants completed SET (χ2 = 4.9, P = .03), with 114 (73.1%) completing 24 months of follow-up in the CBT-I group and 117 (86.7%) in the SET group (χ2 = 8.4, P = .004). After protocol modification, 92 (59.0%) of the CBT-I participants and 86 (63.7%) of the SET participants agreed to extended follow-up (χ2 = 0.7, P = .41), with 81 (51.9%) of the CBT-I participants and 77 (57.0%) of the SET group completing 36 months of follow-up (χ2 = 0.8; P = .39). Incident or recurrent major depression occurred in 19 participants (12.2%) in the CBT-I group and in 35 participants (25.9%) in the SET group, with an overall benefit (hazard ratio, 0.51; 95%, CI 0.29-0.88; P = .02) consistent across subgroups. Remission of insomnia disorder continuously sustained before depression event or during follow-up was more likely in CBT-I participants (41 [26.3%]) compared with the SET participants (26 [19.3%], P = .03). Those in the CBT-I group with sustained remission of insomnia disorder had an 82.6% decreased likelihood of depression (hazard ratio, 0.17; 95%, CI 0.04-0.73; P = .02) compared with those in the SET group without sustained remission of insomnia disorder. Conclusions and relevance The findings of this randomized clinical trial indicate that treatment of insomnia with CBT-I has an overall benefit in the prevention of incident and recurrent major depression in older adults with insomnia disorder. Community-level screening for insomnia concerns in older adults and wide delivery of CBT-I-based treatment for insomnia could substantially advance public health efforts to treat insomnia and prevent depression in this vulnerable older adult population. Trial registration ClinicalTrials.gov Identifier: NCT01641263.